Firuz Baysal

Effects of vitamin E and sodium selenate on neurogenic and endothelial relaxation of corpus cavernosum in the diabetic mouse

We studied the effect of vitamin E and sodium selenate treatment on the neurogenic and endothelium-dependent relaxation of isolated corpus cavernosum obtained from streptozotocin-induced diabetic mice. Relaxant responses of corpus cavernosum precontracted by phenylephrine to electrical field stimulation and to acetylcholine were significantly decreased in diabetic mice. There was no significant difference between diabetic and non-diabetic groups for the relaxant response of corpus cavernosum to sodium nitroprusside and papaverine. Treatment with sodium selenate, but not vitamin E, partially prevented the impairment of the neurogenic relaxation, whereas both had a significant, partial restorative action on endothelial dysfunction in corpus cavernosum obtained from diabetic groups. Neither agent exhibited a significant action on the relaxant responses of corpus cavernosum obtained from non-diabetic mice. A decrease in the sensitivity of the neurogenic impairment to antioxidant action may develop more rapidly than that of endothelial dysfunction in streptozotocin-induced diabetic mice.

An in vitro study of nonadrenergic-noncholinergic activity on the cavernous tissue of mouse

The relaxant effects of electrical field stimulation (EFS) and exogenously applied acetylcholine (ACh) or acidified NaNO2 (a-NaNO2) were investigated in the isolated mouse corpus cavernosum precontracted with phenylephrine hydrochloride (PE). Tetrodotoxin (TTX) blocked the relaxant effects of EFS completely, whereas it had no effect on the responses to ACh or a-NaNO2. Guanethidine and indomethacin failed to affect the electrically or ACh-induced relaxations. Atropine completely blocked the effect of ACh; however, it caused a slight reduction in the relaxation evoked by EFS.NG- Nitro-l-arginine (l-NOARG) reduced the effects of EFS and ACh significantly, but it was ineffective on the relaxations induced by a-NaNO2. The inhibitory action ofl-NOARG was partly restored byl-arginine, but not byd-arginine. Methylene blue (MB) and hydroxocobalamin (HC) exhibited significant inhibition on the relaxations evoked by EFS, ACh and a-NaNO2. Hydroquinone (HQ) reduced relaxation due to a-NaNO2, but did not affect that of EFS and ACh. Our findings suggest that EFS-induced relaxations of mouse cavernosal tissue are mediated by a transmitter which probably resembles an organic nitrate.

The effects of some K+ channel blockers on scopolamine- or electroconvulsive shock-induced amnesia in mice

The effects of three K(+) channel blockers, 4-aminopyridine, 3, 4-diaminopyridine and apamin, on scopolamine- or electroconvulsive shock-induced amnesia were investigated in mice by using a one-trial step-down passive avoidance system. Scopolamine and electroconvulsive shock reduced the retention latency of passive avoidance, which indicated the amnestic effect of these treatments. 4-Aminopyridine, 3,4-diaminopyridine and apamin injected immediately after the acquisition trial, reversed the amnestic effect of scopolamine or electroconvulsive shock in a dose-dependent manner. None of the drugs or electroconvulsive shock treatment affected the rotarod or activity cage performance of the mice. These results indicate that K(+) channel blockers may improve cognitive deficits when memory is impaired by a drug or any other manipulation.

A possible role of S-nitrosothiols at the nitrergic relaxations in the mouse corpus cavernosum

Relaxations induced by electrical field stimulation and acetylcholine were compared with those induced by acidified sodium nitrite, sodium nitroprusside, S-nitrosoglutathione and S-nitroso-N-acetyl-D,L-penicillamine in the mouse corpus cavernosum precontracted with phenylephrine. NG-nitro-L-arginine inhibited electrical field stimulation- or acetylcholine-induced relaxation, but was ineffective on relaxations caused by the other stimuli. Hydroquinone and pyrogallol had no inhibitory action on the relaxations caused by any stimulus except acidified sodium nitrite. Incubation of the tissue with diethyldithiocarbamic acid significantly inhibited the relaxations induced by all stimuli except papaverine. In the tissues pre-treated with diethyldithiocarbamic acid, superoxide dismutase, hydroquinone and pyrogallol failed to yield restore or further inhibit the relaxations in response to electrical field stimulation or acetylcholine. LY 83583 (6-anilino-5,8-quinolinedione) and hydroxocobalamin clearly inhibited the relaxant responses to electrical field stimulation, acetylcholine, S-nitrosoglutathione and acidified sodium nitrite whereas there was significant enhancement of the relaxation produced by S-nitroso-N-acetyl-D,L-penicillamine. These findings suggest that the relaxant factor released from non-adrenergic non-cholinergic nerves or endothelial cells in mouse cavernosal tissue may be a superoxide anion-resistant nitric oxide-containing molecule and that S-nitrosoglutathione rather than S-nitroso-N-acetyl-D,L-penicillamine could be a suitable candidate for this.

Restorative effects of zinc and selenium on nitrergic relaxations impaired by cadmium in the mouse corpus cavernosum.

We investigated whether Cd2+ intake (in drinking water, 15 ppm) for 30 days can affect the nitrergic relaxations of the mouse corpus cavernosum (CC) and whether Zn2+ (25 mg kg(-1) via a stomach tube at 48-h intervals) or sodium selenate (8 microg kg(-1) day(-1) intraperitoneally) has a restorative action on the impairment in the response. Relaxant responses of the CC obtained from Cd2+-treated mice to electrical field stimulation (neurogenic) or acetylcholine (endothelium dependent) were significantly inhibited. A partial restoration was observed in the nitrergic relaxation of the CC obtained from Zn2+- or sodium selenate-co-treated animals. Neither agent exhibited any significant action on the responses of the tissue from control mice. There was no significant difference between Cd2+-treated and control mice in respect of the relaxation amplitude induced by sodium nitroprusside or papaverine. These results suggest that Cd2+ intake may impair the nitrergic relaxation of the mouse CC, and, co-treatment with Zn2+ or sodium selenate may partially improve the nitrergic mechanisms in the tissue.

Possible Stimulation of Na+-K+-ATPase by NO Produced from Sodium Nitrite by Ultraviolet Light in Mouse Gastric Fundal Strip

1. In the present study, we investigated the roles of Na+-K+-ATPase and extracellular Na+ or Ca2+ ions in ultraviolet (UV) light-induced photorelaxation of methacholine-contracted mouse isolated gastric fundus in the presence of NaNO2 (50 microM). 2. Ouabain (1-500 microM), sodium vanadate (10 microM to 3 mM) and amiloride (1-100 microM) completely inhibited the photorelaxation in a concentration-dependent manner. 3. Metabolic inhibitors, sodium azide (10-100 microM), 2,4-dinitrophenol (100 microM to 1 mM) and sodium fluoride (100 microM to 1 mM) significantly reduced photorelaxation. 4. Substitution of sucrose, lithium or KCl with extracellular Na+ completely abolished the photorelaxant responses. 5. Replacement of all extracellular CaCl2 with BaCl2 also completely inhibited UV-induced relaxation. 6. Verapamil (1-10 microM) decreased UV-induced relaxation significantly. 7. These results suggest that nitric oxide produced from NaNO2 by UV-light in mouse gastric fundus probably stimulates Na+-K+-ATPase activity, and photorelaxation of gastric smooth muscle is dependent on extracellular Na+ and Ca2+ ions.

Effects of some catecholamines on the arterial blood pressure of turtle, Testudo graeca

Abstract 1. 1. We have investigated the effects of some catecholamines on the arterial blood pressure of turtle. 2. 2. Epinephrine and norepinephrine induced a slowly developing sustained rise in the blood pressure. Responses were dose dependent. 3. 3. Norepinephrine produced a statistically significant bradycardic effect in high dose. 4. 4. Isoproterenol caused a sustained fall in blood pressure. This drug did not exert any significant effect on the heart rate.

The effects of piracetam on morphine-induced amnesia and analgesia: The possible contribution of central opiatergic mechanisms on the antiamnestic effect of piracetam

The involvement of opiatergic mechanisms on the antiamnestic effects of piracetam was investigated in mice. First, the effects of piracetam and naloxone on the amnesia induced by scopolamine, electroconvulsive shock and morphine were evaluated by using elevated plus maze apparatus. Second, the effects of electroconvulsive shock and piracetam on the antinociceptive action of morphine were tested by means of radiant heat tail-flick experiment. Piracetam and naloxone reversed the drug- or electrically-induced amnestic effects. On the other hand, electroconvulsive shock treatment enhanced the antinociceptive effect of morphine while piracetam decreased the same activity. These results suggest an important role of the opiatergic system on the learning and memory process as well as on the antiamnestic effect of piracetam.

Effects of some divalent cations on nitrergic relaxations in the mouse corpus cavernosum.

Acute effects of some divalent cations (Cd2+, Ni2+, Co2+, Zn2+, Mn2+ and Sn2+) were investigated on neurogenic and endothelium‐dependent relaxations in the isolated mouse corpus cavernosum. Neither neurogenic nor endothelium‐dependent relaxation was affected by cations at the concentrations used (up to 100 μM), except Cd2+. Although Cd2+ (20 and 40 μM) did not cause any significant alteration in the acetylcholine‐ (ACh) or sodium nitroprusside‐ (SNP) induced relaxation, it inhibited electrical field stimulation‐ (EFS) produced relaxation significantly. Zn2+ and selenium could not reverse this inhibitory action. Cd2+ did block the EFS‐evoked guanethidine‐sensitive contraction in the presence of NG‐nitro‐L‐arginine. Elevation of external Ca2+ content significantly reduced the inhibitions due to Cd2+ on the EFS‐induced relaxation and on the EFS‐evoked guanethidine‐sensitive contraction. In the Ca2+‐omitted medium, EFS‐induced relaxation disappeared, while acetylcholine‐elicited relaxation resisted. Verapamil was ineffective on the relaxation produced by EFS or acetylcholine. However, it significantly diminished phenylephrine‐induced contractions. These findings suggest that unlike other cations at the concentrations used in the present study, Cd2+ may have an effect on an external Ca2+‐dependent mechanism at the neuronal level, and this effect may be responsible for its acute inhibitory action on the neurogenic relaxation in the mouse corpus cavernosum.

Molecular mechanism of KCl-induced relaxation of the esophagus

KCl (40 mM) caused reproducible relaxations in frog esophagus. N(G)-nitro-L-arginine (L-NOARG; 1-100 microM), a steriospecific inhibitor of nitric oxide synthase (NOS), completely inhibited the relaxations induced by KCl but not those induced by vasoactive intestinal polypeptide (VIP) antagonist. The inhibitory effect of L-NOARG was prevented by L-arginine (L-ARG; 0.1-1 mM), the precursor of nitric oxide (NO) biosynthesis, but not by D-arginine (D-ARG; 0.1-0.5 mM), the enantiomer of L-arginine. L-ARG or D-ARG alone did not significantly modify the effect of KCl. The relaxations to KCl were significantly inhibited by omega conotoxin (omega-conotoxin; 0.1 microM), a selective blocker of N-type calcium channels. Propranolol (0.1-1 microM), a nonselective blocker of beta-adrenergic receptors, prazosine (0.01-0.1 microM), a selective blocker of alpha(1)-adrenergic receptors, phentolamine (0.1-1 microM), a nonselective blocker of adrenergic receptors, atropine, a selective blocker of muscarinic cholinergic receptors, and lidocaine (1-10 microM), a blocker of sodium channels, had no effect on KCl-evoked relaxations. Caffeine (500 microM), an intracellular calcium releasing agent, did not significantly modify the effect of KCl. In contrast, ruthenium red (100 microM), a selective blocker of ryanodine receptors (intracellular Ca(2+) channels), significantly inhibited these relaxations. Similarly, potassium channel blockers such as 4-aminopyridine (4-AP; 100 microM) and tetraethylammonium (TEA; 100 microM) caused a significant inhibition on relaxations to KCl. In addition, ouabain (100 microM), a specific blocker of Na(+)-K(+)-ATPase, also caused a significant inhibition on these relaxations. The results suggest that NO, Na(+)-K(+)-ATPase and potassium channels may have a role on relaxations induced by 40 mM KCl in the frog esophagus.